Inhibition of human immunodeficiency virus type 1 replication by nuclear chimeric anti-HIV ribozymes in a human T lymphoblastoid cell line. NLM AIDSLINE Important note: Information in this article was accurate in 1998. The state of the art may have changed since the publication date.

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Inhibition of human immunodeficiency virus type 1 replication by nuclear chimeric anti-HIV ribozymes in a human T lymphoblastoid cell line.

Hum Gene Ther. 1998 Mar 20;9(5):621-8. Unique Identifier : AIDSLINE MED/98211332
Michienzi A; Conti L; Varano B; Prislei S; Gessani S; Bozzoni I; Istituto Pasteur, Fondazione Cenci-Bolognetti, Department of Genetics; and Molecular Biology, University La Sapienza, Rome, Italy.

Abstract: Human immunodeficiency virus (HIV) infection represents one of the most challenging systems for gene therapy. Thanks to the extended knowledge of the molecular biology of the HIV life cycle, many different strategies have been developed including transdominant modifications of HIV proteins, RNA decoys, antisense RNA, ribozymes, and intracellular antibody fragments. In this paper, we have tested in a human T lymphoblastoid cell line the antiviral activity of ribozymes specifically designed to co-localize inside the nucleus with the Rev pre-mRNA before it is spliced and transported to the cytoplasm. This result was obtained by inserting the ribozyme in the spliceosomal U1 small nuclear RNA (snRNA) and in a derivative that has perfect complementarity with the 5' splice site of the Rev pre-mRNA. These ribozymes were tested in human T cell clones and were shown to be very efficient in inhibiting viral replication. Not only were the p24 levels in the culture medium drastically reduced but so were the intracellular HIV transcripts. Control disabled ribozymes enabled us to show the specificity of the ribozyme activity. Therefore, these constructs have potential utility for gene therapy of HIV-1 infection.
Keywords: *Anti-HIV Agents/PHARMACOLOGY *HIV-1/DRUG EFFECTS *HIV-1/PHYSIOLOGY *RNA, Catalytic/GENETICS *RNA, Catalytic/PHARMACOLOGY *Virus Replication/DRUG EFFECTSKWDanti-hivagents/pharmacologyKWDhiv-1/drugeffectsKWDhiv-1/physiologyKWDrna,catalytic/geneticsKWDrna,catalytic/pharmacologyKWDvirusreplication/drugeffects
980830
M9881184

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